| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 148, 1065-1074, Copyright © 1996 by American Society for Investigative Pathology
REGULAR ARTICLES |
LF Brown, K Tognazzi, HF Dvorak and TJ Harrist
Department of Pathology, Beth Israel Hospital, Boston, Massachusetts 02215, USA.
Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), plays an important role in the angiogenesis associated with the growth of many human and animal tumors. VPF/VEGF stimulates endothelial cell growth and increases microvascular permeability by interacting with two endothelial cell tyrosine kinase receptors, KDR and flt-1. We studied 16 cases of AIDS-associated Kaposi's sarcoma (KS), 2 cases of cutaneous angiosarcoma, and 6 cases of capillary hemangioma by in situ hybridization for expression of VPF/VEGF, KDR, and flt-1 mRNAs. We also performed immunohistochemical staining for VPF/VEGF protein in 15 cases. Tumor cells in KS and angiosarcoma strongly expressed KDR but not flt-1 mRNA. Endothelial cells in small stromal vessels in and around these tumors strongly expressed both KDR and flt-1 mRNAs. Tumor cells expressed VPF/VEGF mRNA strongly in only one case of KS, adjacent to an area of necrosis. This was also the only case in which the tumor cells stained substantially for VPF/VEGF protein. VPF/VEGF mRNA and protein were, however, strongly expressed by squamous epithelium in areas of hyperplasia and near areas of ulceration overlying tumors. VPF/VEGF mRNA was also expressed focally at lower levels by infiltrating inflammatory cells, probably macrophages. The strong expression of both KDR and flt-1 in small stromal vessels in and around tumors suggests that VPF/VEGF may be an important regulator of the edema and angiogenesis seen in these tumors. The strong expression of KDR by tumor cells in KS and angiosarcoma implies that VPF/VEGF may also have a direct effect on tumor cells. Tumor cells in four of six capillary hemangiomas strongly expressed both KDR and flt-1 mRNAs in contrast to the high level expression of only KDR observed in the malignant vascular tumors studied. Neither VPF/VEGF mRNA or protein were strongly expressed in capillary hemangiomas. VPF/VEGF and its receptors may play an important but as yet incompletely understood role in the pathogenesis of both benign and malignant vascular tumors.
This article has been cited by other articles:
 |
|
 |
|
  K. A. Horvath and Y. Zhou Transmyocardial Laser Revascularization and Extravascular Angiogenetic Techniques to Increase Myocardial Blood Flow Card. Surg. Adult, January 1, 2008; 3(2008): 733 - 752. [Full Text]
|
|
|
|
 |
|
 J Ji and K Hemminki Familial blood vessel tumors and subsequent cancers Ann. Onc., July 1, 2007; 18(7): 1260 - 1267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. R. Rezaee, C. Cunningham, A. J. Davison, and D. J. Blackbourn Kaposi's sarcoma-associated herpesvirus immune modulation: an overview J. Gen. Virol., July 1, 2006; 87(7): 1781 - 1804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Wilgus, A. M. Matthies, K. A. Radek, J. V. Dovi, A. L. Burns, R. Shankar, and L. A. DiPietro Novel Function for Vascular Endothelial Growth Factor Receptor-1 on Epidermal Keratinocytes Am. J. Pathol., November 1, 2005; 167(5): 1257 - 1266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. R. Santos and S. Dias Internal and external autocrine VEGF/KDR loops regulate survival of subsets of acute leukemia through distinct signaling pathways Blood, May 15, 2004; 103(10): 3883 - 3889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Cerimele, L. F. Brown, F. Bravo, G. M. Ihler, P. Kouadio, and J. L Arbiser Infectious Angiogenesis: Bartonella bacilliformis Infection Results in Endothelial Production of Angiopoetin-2 and Epidermal Production of Vascular Endothelial Growth Factor Am. J. Pathol., October 1, 2003; 163(4): 1321 - 1327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Chhokar and A. L. Tucker Angiogenesis: Basic Mechanisms and Clinical Applications Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2003; 7(3): 253 - 280. [Abstract] [PDF]
|
|
|
|
 |
|
 H. F. Dvorak Vascular Permeability Factor/Vascular Endothelial Growth Factor: A Critical Cytokine in Tumor Angiogenesis and a Potential Target for Diagnosis and Therapy J. Clin. Oncol., November 1, 2002; 20(21): 4368 - 4380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ruel, R. J. Laham, J. A. Parker, M. J. Post, J. A. Ware, M. Simons, and F. W. Sellke Long-term effects of surgical angiogenic therapy with fibroblast growth factor 2 protein J. Thorac. Cardiovasc. Surg., July 1, 2002; 124(1): 28 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. BRENNER, N. R. NAYAK, O. D. SLAYDEN, H. O. D. CRITCHLEY, and R. W. KELLY Premenstrual and Menstrual Changes in the Macaque and Human Endometrium: Relevance to Endometriosis Ann. N.Y. Acad. Sci., March 1, 2002; 955(1): 60 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. W. Jackson, J. S. Roberts, S. E. Heckford, C. Ricciardelli, J. Stahl, D. J. Horsfall, and W. D. Tilley A Potential Autocrine Role for Vascular Endothelial Growth Factor in Prostate Cancer Cancer Res., February 1, 2002; 62(3): 854 - 859. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Post, R. Laham, F. W. Sellke, and M. Simons Therapeutic angiogenesis in cardiology using protein formulations Cardiovasc Res, February 16, 2001; 49(3): 522 - 531. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. R. Nayak, H. O. D. Critchley, O. D. Slayden, A. Menrad, K. Chwalisz, D. T. Baird, and R. M. Brenner Progesterone Withdrawal Up-Regulates Vascular Endothelial Growth Factor Receptor Type 2 in the Superficial Zone Stroma of the Human and Macaque Endometrium: Potential Relevance to Menstruation J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3442 - 3452. [Abstract] [Full Text]
|
|
|
|
|
|
L. F. Brown, B. J. Dezube, K. Tognazzi, H. F. Dvorak, and G. D. Yancopoulos Expression of Tie1, Tie2, and Angiopoietins 1, 2, and 4 in Kaposi's Sarcoma and Cutaneous Angiosarcoma Am. J. Pathol., June 1, 2000; 156(6): 2179 - 2183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Arbiser, H. Larsson, L. Claesson-Welsh, X. Bai, K. LaMontagne, S. W. Weiss, S. Soker, E. Flynn, and L. F. Brown Overexpression of VEGF 121 in Immortalized Endothelial Cells Causes Conversion to Slowly Growing Angiosarcoma and High Level Expression of the VEGF Receptors VEGFR-1 and VEGFR-2 in Vivo Am. J. Pathol., April 1, 2000; 156(4): 1469 - 1476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Arastéh and A. Hannah The Role of Vascular Endothelial Growth Factor (VEGF) in AIDS-Related Kaposi's Sarcoma Oncologist, April 1, 2000; 5(90001): 28 - 31. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. K. Gupta, V. Ruvolo, C. Patterson, and S. Swaminathan The Human Herpesvirus 8 Homolog of Epstein-Barr Virus SM Protein (KS-SM) Is a Posttranscriptional Activator of Gene Expression J. Virol., January 1, 2000; 74(2): 1038 - 1044. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Aoki and G. Tosato Role of Vascular Endothelial Growth Factor/Vascular Permeability Factor in the Pathogenesis of Kaposi's Sarcoma-Associated Herpesvirus-Infected Primary Effusion Lymphomas Blood, December 15, 1999; 94(12): 4247 - 4254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tomlinson, S. H. Barsky, S. Nelson, S. Singer, B. Pezeshki, M. C. Lee, F. Eilber, and M. Nguyen Different Patterns of Angiogenesis in Sarcomas and Carcinomas Clin. Cancer Res., November 1, 1999; 5(11): 3516 - 3522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Garlanda and E. Dejana Heterogeneity of Endothelial Cells : Specific Markers Arterioscler. Thromb. Vasc. Biol., July 1, 1997; 17(7): 1193 - 1202. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Masood, J. Cai, T. Zheng, D. L. Smith, Y. Naidu, and P. S. Gill Vascular endothelial growth factor/vascular permeability factor is an autocrine growth factor for AIDS-Kaposi sarcoma PNAS, February 4, 1997; 94(3): 979 - 984. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
